Method and Apparatus for Detecting False Hypoglycemic Conditions

ABSTRACT

Embodiments of the present disclosure include detecting a concurrent occurrence of a decrease in monitored analyte level and a corresponding decrease in monitored on-skin temperature, confirming a presence of an impending hypoglycemic condition, and asserting a notification corresponding to the confirmed impending hypoglycemic condition. Devices, methods, systems and kits incorporating the same are also provided.

RELATED APPLICATION

The present application is a continuation of U.S. patent applicationSer. No. 13/477,026 filed May 21, 2012, now U.S. Pat. No. 9,050,041,which is a divisional of U.S. patent application Ser. No. 12/916,481filed Oct. 29, 2010, now U.S. Pat. No. 8,185,181, which claims thebenefit of U.S. Provisional Application No. 61/256,920 filed Oct. 30,2009, entitled “Method and Apparatus for Detecting False HypoglycemicConditions”, the disclosures of each of which are incorporated herein byreference for all purposes.

BACKGROUND

For diabetic patients, it is desirable and often necessary to detectsymptoms related to hypoglycemic condition, or the onset of suchcondition. If not treated in a timely manner, hypoglycemia (or commonlyassociated with low blood sugar level and sometimes referred to as“insulin shock”) will have detrimental if not lethal effect on thepatient. As insulin therapy becomes more prevalent for the treatment ofdiabetes mellitus, the detection of the onset of such conditions issignificant.

When a diabetic person experiences hypoglycemic condition, often, theperson will experience increased heart rate, perspiration, involuntaryshaking, rapid decline in body temperature, paleness, and over thecourse of a period of hours, the declining blood sugar level may impactthe brain functions, potentially resulting in dizziness, hindered bodilycoordination, undesirable modification in behavior and the like. Deathor permanent brain damage is not uncommon if the declining blood sugarlevel is left untreated.

Commercially available continuous glucose monitoring systems providetools for diabetic patients to continuously monitor the glucose levelsand provide on-going feedback to the patient to take corrective action.Such systems use glucose sensors which at times exhibit inaccuracies.That is, there are times when the glucose sensor may falsely indicate alow glucose reading, triggering a false warning to the user. The falseindications, sometimes referred to as sensor signal dropouts, may beattributable to a variety of factors, such as inherent inaccuracies inthe system, the instability of the sensor during the initial time periodof use, changes in the sensor's environment, pressure on a blood vesselsupplying glucose to the tissue in which the sensor is implanted, noisein the system, and the like. It has been found that such false positiveindication of low glucose readings generated by the sensor in use occurmore often during night time. This in turn causes a significantinconvenience or disadvantage to the user or the patient if alarms ornotifications are associated with low glucose measurements and aretriggered during night time, when in fact the glucose level of thepatient or the user is not low and the triggered alarm or notificationwas a false alarm.

SUMMARY

In view of the foregoing, in aspects of the present disclosure, methods,systems, apparatus and kits are provided which reduce the occurrence offalse alarms or notifications to the user associated with falsehypoglycemic condition detection based on data from analyte sensors. Inparticular, in aspects of the present disclosure, a user's glucose levelis monitored in conjunction with the temperature and/or perspirationlevel of the patient, and the fluctuations of the glucose level and thetemperature and/or perspiration level is monitored such that, when apotential hypoglycemic condition or a potential impending hypoglycemiccondition is detected, the presence of such potential conditions isconfirmed before the associated notification or alarm is asserted.

In addition to the monitored temperature or perspiration level, withinthe scope of the present disclosure, other physiological parameters maybe monitored for confirming the presence of hypoglycemic condition, suchas, for example, a user's heart rate, detected tremor, or oxygensaturation level of the user's blood.

A method in accordance with one embodiment includes receiving aplurality of time spaced analyte related data monitored by an analytesensor in fluid contact with an analyte during a first time period,detecting when one or more of the received plurality of time spacedanalyte related data crosses a predetermined analyte threshold levelduring the first time period, receiving a plurality of time spacedtemperature data during the first time period, determining a rate ofchange of the received plurality of time spaced temperature data anddetecting when the determined rate of change crosses a predeterminedrate of temperature change; and asserting a notification when thedetermined rate of change of the received plurality of the time spacedtemperature data reaches the predetermined rate of temperature changeand when the one or more of the received plurality of time spacedanalyte related data reaches the predetermined threshold analyte levelduring the first time period.

A method in accordance with another embodiment includes receiving aplurality of time spaced analyte related data monitored by an analytesensor in fluid contact with an analyte during a first time period,detecting when one or more of the received plurality of time spacedanalyte related data reaches a predetermined analyte threshold levelduring the first time period, receiving a plurality of time spacedtemperature data during the first time period, detecting when one ormore of the time spaced temperature related data crosses a predeterminedthreshold temperature level during the first time period, and assertinga notification when the one or more of the received plurality of timespaced analyte related data reaches a predetermined threshold analytelevel and when the one or more of the plurality of time spacedtemperature related data reaches the predetermined temperature thresholdlevel during the first time period.

In still another aspect, a method in accordance with certain embodimentsof the present disclosure includes monitoring a variation in on-skintemperature in proximity to a transcutaneously positioned analyte sensorhaving at least a portion in fluid contact with an analyte during amonitoring time period, detecting the variation in the monitoredtemperature exceeding a predetermined threshold level, confirming apresence of a medically significant condition when the detectedvariation in the monitored temperature exceeds the predeterminedthreshold level, and asserting a notification associated with themedically significant condition when it is confirmed, wherein confirmingthe presence of the medically significant condition includes determininga variation in the monitored analyte level exceeding the predeterminedthreshold level based on comparing a slope indicative of the change inthe monitored analyte level substantially to a slope indicative of thechange in the monitored on-skin temperature variation.

A method in still another embodiment includes detecting a concurrentoccurrence of a decrease in monitored analyte level and a correspondingdecrease in monitored on-skin temperature, confirming a presence of animpending hypoglycemic condition, and asserting a notificationcorresponding to the confirmed impending hypoglycemic condition.

A method of confirming hypoglycemic condition in a patient in yet stilla further embodiment includes monitoring a directional change in glucoselevel based on data stream received from an analyte sensor during amonitoring time period, monitoring a directional change in a firstphysiological parameter during the monitoring time period, monitoring adirectional change in a second physiological parameter during themonitoring time period, detecting an initialization of a hypoglycemicalarm based, at least in part, on the directional change of themonitored glucose level, and comparing the directional change in one ormore of the first or the second physiological parameters relative to thedirectional change in the glucose level prior to the assertion of thehypoglycemic alarm.

An apparatus in accordance with one embodiment includes one or moreprocessors, and a memory for storing instructions which, when executedby the one or more processors, causes the one or more processors toreceive a plurality of time spaced analyte related data monitored by ananalyte sensor in fluid contact with an analyte during a first timeperiod, determine a rate of change of the received plurality of timespaced analyte related data, receive a plurality of time spacedtemperature data during the first time period, determine a rate ofchange of the received plurality of time spaced temperature data,compare the determined rate of change of the received plurality of thetime spaced temperature data to the predetermined threshold level whenthe determined rate of change of the received plurality of time spacedanalyte related data exceeds a predetermined threshold level, and asserta notification when the determined rate of change of the receivedplurality of the time spaced temperature data exceeds the predeterminedthreshold level.

An apparatus in accordance with still another aspect includes one ormore processors, and a memory for storing instructions which, whenexecuted by the one or more processors, causes the one or moreprocessors to monitor a variation in on-skin temperature in proximity toa transcutaneously positioned analyte sensor having at least a portionin fluid contact with an analyte during a monitoring time period, detectthe variation in the monitored temperature exceeding a predeterminedthreshold level, confirm a presence of a medically significant conditionwhen the detected variation in the monitored temperature exceeds thepredetermined threshold level, and assert a notification associated withthe medically significant condition when it is confirmed, wherein thememory for storing instructions which, when executed by the one or moreprocessors, causes the one or more processors to determine a variationin the monitored analyte level exceeding the predetermined thresholdlevel based on comparing a slope indicative of the change in themonitored analyte level substantially to a slope indicative of thechange in the monitored on-skin temperature variation.

An apparatus in accordance with still another aspect includes one ormore processors, and a memory for storing instructions which, whenexecuted by the one or more processors, causes the one or moreprocessors to detect a concurrent occurrence of a decrease in monitoredanalyte level and a corresponding decrease in monitored on-skintemperature, confirm a presence of an impending hypoglycemic condition,and assert a notification corresponding to the confirmed impendinghypoglycemic condition.

An apparatus in still yet a further embodiment includes one or moreprocessors, and a memory for storing instructions which, when executedby the one or more processors, causes the one or more processors tomonitor a directional change in glucose level based on data streamreceived from an analyte sensor during a monitoring time period, monitora directional change in a first physiological parameter during themonitoring time period, monitor a directional change in a secondphysiological parameter during the monitoring time period, detect aninitialization of a hypoglycemic alarm based, at least in part, on thedirectional change of the monitored glucose level, and compare thedirectional change in one or more of the first or the secondphysiological parameters relative to the directional change in theglucose level prior to the assertion of the hypoglycemic alarm.

In this manner, in aspects of the present disclosure, the occurrence offalse notifications associated with the presence of hypoglycemiccondition, impending hypoglycemic condition, or onset of hypoglycemiccondition is reduced, providing robustness to the glucose monitoringsystem.

These and other features, objects and advantages of the presentdisclosure will become apparent to those persons skilled in the art uponreading the details of the present disclosure as more fully describedbelow.

BRIEF DESCRIPTION OF THE DRAWINGS

A detailed description of various aspects, features and embodiments ofthe present disclosure is provided herein with reference to theaccompanying drawings, which are briefly described below. The drawingsare illustrative and are not necessarily drawn to scale, with somecomponents and features being exaggerated for clarity. The drawingsillustrate various aspects or features of the present disclosure and mayillustrate one or more embodiment(s) or example(s) of the presentdisclosure in whole or in part. A reference numeral, letter, and/orsymbol that is used in one drawing to refer to a particular element orfeature may be used in another drawing to refer to a like element orfeature. Included in the drawings are the following:

FIG. 1 shows a block diagram of an embodiment of a data monitoring andmanagement system with which a sensor according to the presentdisclosure is usable;

FIG. 2 shows a block diagram of an embodiment of the data processingunit of the data monitoring and management system of FIG. 1;

FIG. 3 shows a block diagram of an embodiment of the receiver/monitorunit of the data monitoring and management system of FIG. 1;

FIG. 4 is a flowchart illustrating a routine associated with determiningfalse signal attenuation of an analyte sensor in one aspect of thepresent disclosure;

FIG. 5 is a flowchart illustrating a routine associated with determiningfalse signal attenuation of an analyte sensor in another aspect of thepresent disclosure;

FIG. 6 is a flowchart illustrating a routine associated with determiningfalse signal attenuation of an analyte sensor in a further aspect of thepresent disclosure;

FIG. 7 is graphical illustration of the monitored glucose level and thecorresponding temperature level during the same time period confirming ahypoglycemic event; and

FIG. 8 is a graphical illustration of the monitored glucose level andthe corresponding temperature level during the same time periodindicating a false hypoglycemic event.

INCORPORATION BY REFERENCE

Patents, applications and/or publications described herein, includingthe following patents, applications and/or publications are incorporatedherein by reference for all purposes: U.S. Pat. Nos. 4,545,382,4,711,245, 5,262,035, 5,262,305, 5,264,104, 5,320,715, 5,356,786,5,509,410, 5,543,326, 5,593,852, 5,601,435, 5,628,890, 5,820,551,5,822,715, 5,899,855, 5,918,603, 6,071,391, 6,103,033, 6,120,676,6,121,009, 6,134,461, 6,143,164, 6,144,837, 6,161,095, 6,175,752,6,270,455, 6,284,478, 6,299,757, 6,338,790, 6,377,894, 6,461,496,6,503,381, 6,514,460, 6,514,718, 6,540,891, 6,560,471, 6,579,690,6,591,125, 6,592,745, 6,600,997, 6,605,200, 6,605,201, 6,616,819,6,618,934, 6,650,471, 6,654,625, 6,676,816, 6,730,200, 6,736,957,6,746,582, 6,749,740, 6,764,581, 6,773,671, 6,881,551, 6,893,545,6,932,892, 6,932,894, 6,942,518, 7,041,468, 7,167,818, and 7,299,082,U.S. Published Application Nos. 2004/0186365, now U.S. Pat. No.7,811,231, 2005/0182306, now U.S. Pat. No. 8,771,183, 2006/0025662, nowU.S. Pat. No. 7,740,581, 2006/0091006, 2007/0056858, now U.S. Pat. No.8,298,389, 2007/0068807, now U.S. Pat. No. 7,846,311, 2007/0095661,2007/0108048, now U.S. Pat. No. 7,918,975, 2007/0199818, now U.S. Pat.No. 7,811,430, 2007/0227911, now U.S. Pat. No. 7,887,682, 2007/0233013,2008/0066305, now U.S. Pat. No. 7,895,740, 2008/0081977, now U.S. Pat.No. 7,618,369, 2008/0102441, now U.S. Pat. No. 7,822,557, 2008/0148873,now U.S. Pat. No. 7,802,467, 2008/0161666, 2008/0267823, and2009/0054748, now U.S. Pat. No. 7,885,698, U.S. patent application Ser.Nos. 11/461,725, now U.S. Pat. No. 7,866,026, Ser. Nos. 12/131,012,12/393,921, 12/242,823, now U.S. Pat. No. 8,219,173, Ser. No.12/363,712, now U.S. Pat. No. 8,346,335, Ser. Nos. 12/495,709,12/698,124, 12/698,129, 12/714,439, 12/794,721, now U.S. Pat. No.8,595,607, Ser. Nos. 12/807,278, 12/842,013, and 12/871,901, now U.S.Pat. No. 8,514,086, and U.S. Provisional Application Nos. 61/238,646,61/246,825, 61/247,516, 61/249,535, 61/317,243, 61/345,562, 61/325,260and 61/361,374.

DETAILED DESCRIPTION

Before the present disclosure is described, it is to be understood thatthis disclosure is not limited to particular embodiments described, assuch may, of course, vary. It is also to be understood that theterminology used herein is for the purpose of describing particularembodiments only, and is not intended to be limiting, since the scope ofthe present disclosure will be limited only by the appended claims.

Where a range of values is provided, it is understood that eachintervening value, to the tenth of the unit of the lower limit unlessthe context clearly dictates otherwise, between the upper and lowerlimit of that range and any other stated or intervening value in thatstated range, is encompassed within the disclosure. The upper and lowerlimits of these smaller ranges may independently be included in thesmaller ranges as also encompassed within the disclosure, subject to anyspecifically excluded limit in the stated range. Where the stated rangeincludes one or both of the limits, ranges excluding either or both ofthose included limits are also included in the disclosure.

It must be noted that as used herein and in the appended claims, thesingular forms “a”, “an”, and “the” include plural referents unless thecontext clearly dictates otherwise.

As will be apparent to those of skill in the art upon reading thisdisclosure, each of the individual embodiments described and illustratedherein has discrete components and features which may be readilyseparated from or combined with the features of any of the other severalembodiments without departing from the scope or spirit of the presentdisclosure.

Generally, embodiments of the present disclosure relate to methods anddevices for detecting at least one analyte, such as glucose, in bodyfluid. Embodiments relate to the continuous and/or automatic in vivomonitoring of the level of one or more analytes using a continuousanalyte monitoring system that includes an analyte sensor for the invivo detection, of an analyte, such as glucose, lactate, and the like,in a body fluid. Embodiments include wholly implantable analyte sensorsand analyte sensors in which only a portion of the sensor is positionedunder the skin and a portion of the sensor resides above the skin, e.g.,for contact to a control unit, transmitter, receiver, transceiver,processor, etc. At least a portion of a sensor may be, for example,subcutaneously positionable in a patient for the continuous orsemi-continuous monitoring of a level of an analyte in a patient'sinterstitial fluid. For the purposes of this description,semi-continuous monitoring and continuous monitoring will be usedinterchangeably, unless noted otherwise.

The sensor response may be correlated and/or converted to analyte levelsin blood or other fluids. In certain embodiments, an analyte sensor maybe positioned in contact with interstitial fluid to detect the level ofglucose, which may be used to infer the glucose level in the patient'sbloodstream. Analyte sensors may be insertable into a vein, artery, orother portion of the body containing fluid. Embodiments of the analytesensors of the subject disclosure may be configured for monitoring thelevel of the analyte over a time period which may range from minutes,hours, days, weeks, or longer.

In aspects of the present disclosure, temperature, perspiration or othercharacteristics of a patient such as, for example, other measurablecharacteristics are monitored concurrently with the monitored analytelevel, and used to, in one embodiment, either confirm or rejectnotifications associated with the medically significant condition suchas the onset or impending hypoglycemic condition initially detectedbased on the monitored analyte level.

In one aspect, the hypoglycemic condition may be associated with a lowblood glucose level such as, for example, 40-50 mg/dL or less (dependingupon, for example, age, gender, and the like). Accordingly, alarms ornotifications may be configured, as a default setting or programmedspecific to each patient, to be triggered when the monitored glucoselevel decreases at a rate that approaches the hypoglycemic conditionwithin a defined time period to enable the patient or the user (or thehealthcare provider) to timely take corrective actions. For example,each alarm or notification may be programmed to be asserted or triggeredwhen the monitored glucose level reaches approximately 80 to 100 mg/dL,and decreasing at a rate of 2 mg/dL/minute or more. Referring now to theFigures, an exemplary overall analyte monitoring system including thevarious components is described below.

FIG. 1 illustrates a data monitoring and management system such as, forexample, an analyte (e.g., glucose) monitoring system 100 in accordancewith certain embodiments. Embodiments of the subject disclosure arefurther described primarily with respect to glucose monitoring devicesand systems, and methods of glucose detection, for convenience only andsuch description is in no way intended to limit the scope of thedisclosure. It is to be understood that the analyte monitoring systemmay be configured to monitor a variety of analytes instead of or inaddition to glucose, e.g., at the same time or at different times.

Analytes that may be monitored include, but are not limited to, acetylcholine, amylase, bilirubin, cholesterol, chorionic gonadotropin,creatine kinase (e.g., CK-MB), creatine, creatinine, DNA, fructosamine,glucose, glutamine, growth hormones, hormones, ketone bodies, lactate,oxygen, peroxide, prostate-specific antigen, prothrombin, RNA, thyroidstimulating hormone, and troponin. The concentration of drugs, such as,for example, antibiotics (e.g., gentamicin, vancomycin, and the like),digitoxin, digoxin, drugs of abuse, theophylline, and warfarin, may alsobe monitored. In those embodiments that monitor more than one analyte,the analytes may be monitored at the same or different times.

The analyte monitoring system 100 includes a sensor 101, a dataprocessing unit 102 connectable to the sensor 101, and a primaryreceiver unit 104 which is configured to communicate with the dataprocessing unit 102 via a communication link 103. In certainembodiments, the primary receiver unit 104 may be further configured totransmit data to a data processing terminal 105 to evaluate or otherwiseprocess or format data received by the primary receiver unit 104. Thedata processing terminal 105 may be configured to receive data directlyfrom the data processing unit 102 via a communication link which mayoptionally be configured for bi-directional communication. Further, thedata processing unit 102 may include a transmitter or a transceiver totransmit and/or receive data to and/or from the primary receiver unit104 and/or the data processing terminal 105 and/or optionally thesecondary receiver unit 106.

The electrochemical sensors of the present disclosure may employ anysuitable measurement technique, e.g., may detect current, may employpotentiometry, etc. Techniques may include, but are not limited to,amperometry, coulometry, and voltammetry. In some embodiments, sensingsystems may be optical, colorimetric, and the like.

Also shown in FIG. 1 is an optional secondary receiver unit 106 which isoperatively coupled to the communication link 103 and configured toreceive data transmitted from the data processing unit 102. Thesecondary receiver unit 106 may be configured to communicate with theprimary receiver unit 104, as well as the data processing terminal 105.The secondary receiver unit 106 may be configured for bi-directionalwireless communication with each of the primary receiver unit 104 andthe data processing terminal 105. As discussed in further detail below,in certain embodiments the secondary receiver unit 106 may be ade-featured receiver as compared to the primary receiver unit 104, i.e.,the secondary receiver unit 106 may include a limited or minimal numberof functions and features as compared with the primary receiver unit104. As such, the secondary receiver unit 106 may include a smaller (inone or more, including all, dimensions), compact housing or embodied ina device such as a wrist watch, arm band, etc., for example.

Alternatively, the secondary receiver unit 106 may be configured withthe same or substantially similar functions and features as the primaryreceiver unit 104. The secondary receiver unit 106 may include a dockingportion to be mated with a docking cradle unit for placement by, e.g.,the bedside for nighttime monitoring, and/or a bi-directionalcommunication device. A docking cradle may recharge a power supply.

Only one sensor 101, data processing unit 102 and data processingterminal 105 are shown in the embodiment of the analyte monitoringsystem 100 illustrated in FIG. 1. However, it will be appreciated by oneof ordinary skill in the art that the analyte monitoring system 100 mayinclude more than one sensor 101 and/or more than one data processingunit 102, and/or more than one data processing terminal 105. Multiplesensors may be positioned in a patient for analyte monitoring at thesame or different times. In certain embodiments, analyte informationobtained by a first positioned sensor may be employed as a comparison toanalyte information obtained by a second sensor. This may be useful toconfirm or validate analyte information obtained from one or both of thesensors. Such redundancy may be useful if analyte information iscontemplated in critical therapy-related decisions.

The analyte monitoring system 100 may be a continuous monitoring systemor semi-continuous. In a multi-component environment, each component maybe configured to be uniquely identified by one or more of the othercomponents in the system so that communication conflict may be readilyresolved between the various components within the analyte monitoringsystem 100. For example, unique identification codes (IDs),communication channels, and the like, may be used.

In certain embodiments, the sensor 101 is physically positioned inand/or on the body of a user whose analyte level is being monitored. Thesensor 101 may be configured to continuously or semi-continuously samplethe analyte level of the user automatically (without the user initiatingthe sampling), based on a programmed interval such as, for example, butnot limited to, once every minute, once every five minutes and so on,and convert the sampled analyte level into a corresponding signal fortransmission by the data processing unit 102. The data processing unit102 is coupleable to the sensor 101 so that both devices are positionedin or on the user's body, with at least a portion of the analyte sensor101 positioned transcutaneously. The data processing unit may include afixation element such as adhesive or the like to secure it to the user'sbody. A mount (not shown) attachable to the user and mateable with theunit 102 may be used. For example, a mount may include an adhesivesurface. The data processing unit 102 performs data processingfunctions, where such functions may include, but are not limited to,filtering and encoding of data signals, each of which corresponds to asampled analyte level of the user, for transmission to the primaryreceiver unit 104 via the communication link 103. In one embodiment, thesensor 101 or the data processing unit 102 or a combined sensor/dataprocessing unit may be wholly implantable under the skin layer of theuser.

In certain embodiments, the primary receiver unit 104 may include asignal interface section including an RF receiver and an antenna that isconfigured to communicate with the data processing unit 102 via thecommunication link 103, and a data processing section for processing thereceived data from the data processing unit 102 such as data decoding,error detection and correction, data clock generation, data bitrecovery, etc., or any combination thereof.

In operation, the primary receiver unit 104 in certain embodiments isconfigured to synchronize with the data processing unit 102 to uniquelyidentify the data processing unit 102, based on, for example, anidentification information of the data processing unit 102, andthereafter, to continuously or semi-continuously receive signalstransmitted from the data processing unit 102 associated with themonitored analyte levels detected by the sensor 101. Referring again toFIG. 1, the data processing terminal 105 may include a personalcomputer, a portable computer such as a laptop or a handheld device(e.g., personal digital assistants (PDAs), telephone such as a cellularphone (e.g., a multimedia and Internet-enabled mobile phone such as aniPhone, Blackberry device or similar phone), mp3 player, pager, globalposition system (GPS)) drug delivery device, each of which may beconfigured for data communication with the receiver via a wired or awireless connection. Additionally, the data processing terminal 105 mayfurther be connected to a data network (not shown) for storing,retrieving, updating, and/or analyzing data corresponding to thedetected analyte level of the user.

The data processing terminal 105 may include an infusion device such asan insulin infusion pump or the like, which may be configured toadminister insulin to patients, and which may be configured tocommunicate with the primary receiver unit 104 for receiving, amongothers, the measured analyte level. Alternatively, the primary receiverunit 104 may be configured to integrate an infusion device therein sothat the primary receiver unit 104 is configured to administer insulin(or other appropriate drug) therapy to patients, for example, foradministering and modifying basal profiles, as well as for determiningappropriate boluses for administration based on, among others, thedetected analyte levels received from the data processing unit 102. Aninfusion device may be an external device or an internal device (whollyimplantable in a user).

In certain embodiments, the data processing terminal 105, which mayinclude an insulin pump, may be configured to receive the analytesignals from the data processing unit 102, and thus, incorporate thefunctions of the primary receiver unit 104 including data processing formanaging the patient's insulin therapy and analyte monitoring. Incertain embodiments, the communication link 103 as well as one or moreof the other communication interfaces shown in FIG. 1, may use one ormore of an RF communication protocol, an infrared communicationprotocol, a Bluetooth® enabled communication protocol, an 802.11xwireless communication protocol, or an equivalent wireless communicationprotocol which would allow secure, wireless communication of severalunits (for example, per HIPAA requirements), while avoiding potentialdata collision and interference.

FIG. 2 shows a block diagram of an embodiment of a data processing unitof the data monitoring and detection system shown in FIG. 1. The dataprocessing unit 102 thus may include one or more of an analog interface201 configured to communicate with the sensor 101 (FIG. 1), a user input202, and a temperature measurement section 203, each of which isoperatively coupled to a processor 204 such as a central processing unit(CPU). User input and/or interface components may be included or a dataprocessing unit may be free of user input and/or interface components.In certain embodiments, one or more application-specific integratedcircuits (ASIC) may be used to implement one or more functions orroutines associated with the operations of the data processing unit(and/or receiver unit) using for example one or more state machines andbuffers.

Further shown in FIG. 2 are a transmitter serial communication section205 and an RF transmitter 206, each of which is also operatively coupledto the processor 204. The RF transmitter 206, in some embodiments, maybe configured as an RF receiver or an RF transmitter/receiver, such as atransceiver, to transmit and/or receive data signals. Moreover, a powersupply 207, such as a battery, may also be provided in the dataprocessing unit 102 to provide the necessary power for the dataprocessing unit 102. Additionally, as can be seen from the Figure, clock208 may be provided to, among others, supply real time information tothe processor 204.

As can be seen in the embodiment of FIG. 2, the sensor 101 (FIG. 1)includes four contacts, three of which are electrodes—working electrode(W) 210, guard contact (G) 211, reference electrode (R) 212, and counterelectrode (C) 213, each operatively coupled to the analog interface 201of the data processing unit 102. In certain embodiments, each of theworking electrode (W) 210, guard contact (G) 211, reference electrode(R) 212, and counter electrode (C) 213 may be made using a non-corrodingconductive material that may be applied by, e.g., chemical vapordeposition (CVD), physical vapor deposition, sputtering, reactivesputtering, printing, coating, ablating (e.g., laser ablation),painting, dip coating, etching, and the like. Materials include, but arenot limited to, carbon (such as graphite), gold, iridium, ruthenium,palladium, platinum, rhenium, rhodium, silver, mixtures thereof, andalloys thereof, and metallic oxides, like ruthenium dioxide or iridiumdioxide, of these elements.

In certain embodiments, a unidirectional input path is established fromthe sensor 101 (FIG. 1) and/or manufacturing and testing equipment tothe analog interface 201 of the data processing unit 102, while aunidirectional output is established from the output of the RFtransmitter 206 of the data processing unit 102 for transmission to theprimary receiver unit 104. In this manner, a data path is shown in FIG.2 between the aforementioned unidirectional input and output via adedicated link 209 from the analog interface 201 to serial communicationsection 205, thereafter to the processor 204, and then to the RFtransmitter 206. As such, in certain embodiments, via the data pathdescribed above, the data processing unit 102 is configured to transmitto the primary receiver unit 104 (FIG. 1), via the communication link103 (FIG. 1), processed and encoded data signals received from thesensor 101 (FIG. 1). Additionally, the unidirectional communication datapath between the analog interface 201 and the RF transmitter 206discussed above allows for the configuration of the data processing unit102 for operation upon completion of the manufacturing process as wellas for direct communication for diagnostic and testing purposes.

The processor 204 may be configured to transmit control signals to thevarious sections of the data processing unit 102 during the operation ofthe data processing unit 102. In certain embodiments, the processor 204also includes memory (not shown) for storing data such as theidentification information for the data processing unit 102, as well asthe data signals received from the sensor 101. The stored informationmay be retrieved and processed for transmission to the primary receiverunit 104 under the control of the processor 204. Furthermore, the powersupply 207 may include a commercially available battery.

The data processing unit 102 is also configured such that the powersupply section 207 is capable of providing power to the data processingunit 102 for a minimum period of time, e.g., at least about one month,e.g., at least about three months or more, of continuous operation. Theminimum time period may be after (i.e., in addition to), a period oftime, e.g., up to about eighteen months, of being stored in a low- orno-power (non-operating) mode. In certain embodiments, this may beachieved by the processor 204 operating in low power modes in thenon-operating state, for example, drawing no more than minimal current,e.g., approximately 1 μA of current or less. In certain embodiments, amanufacturing process of the data processing unit 102 may place the dataprocessing unit 102 in the lower power, non-operating state (i.e.,post-manufacture sleep mode). In this manner, the shelf life of the dataprocessing unit 102 may be significantly improved. Moreover, as shown inFIG. 2, while the power supply unit 207 is shown as coupled to theprocessor 204, and as such, the processor 204 is configured to providecontrol of the power supply unit 207, it should be noted that within thescope of the present disclosure, the power supply unit 207 is configuredto provide the necessary power to each of the components of the dataprocessing unit 102 shown in FIG. 2.

Referring back to FIG. 2, the power supply section 207 of the dataprocessing unit 102 in one embodiment may include a rechargeable batteryunit that may be recharged by a separate power supply recharging unit(for example, provided in the receiver unit 104) so that the dataprocessing unit 102 may be powered for a longer period of usage time. Incertain embodiments, the data processing unit 102 may be configuredwithout a battery in the power supply section 207, in which case thedata processing unit 102 may be configured to receive power from anexternal power supply source (for example, a battery, electrical outlet,etc.) as discussed in further detail below.

Referring yet again to FIG. 2, a temperature detection section 203 ofthe data processing unit 102 is configured to monitor the temperature ofthe skin near the sensor insertion site. The temperature reading may beused to adjust the analyte readings obtained from the analog interface201. In a further aspect, the temperature measurement or readinggenerated from the temperature detection section 203 may be used inconjunction with the received analyte data to determine or confirm amonitored condition such as an impending or onset of hypoglycemiccondition as discussed in further detail below. For example, thetemperature measurement section may include a thermistor to monitor theon-skin (or ambient) temperature in direct or indirect contact with thepatient's skin. Example embodiments of temperature measurement sectionare provided in, for example, U.S. Pat. No. 6,175,752, and applicationSer. No. 11/026,766 entitled “Method and Apparatus for ProvidingTemperature Sensor Module in a Data Communication System,” each assignedto the assignee of the present application, and the disclosure of eachof which are incorporated herein by reference for all purposes.

In a further embodiment, the temperature measurement or reading may begenerated or determined from a different area of the body such as theear canal, rectum, mouth, other body cavity, or forehead using asuitable temperature measuring device or components which incorporatethe temperature measurement functionalities and capable of transmitting(wirelessly or via wired connection) the determined temperatureinformation to the receiver unit 104/106 (FIG. 1) and/or data processingterminal/infusion section 105 (FIG. 1) for further processing.

Referring back to FIG. 2, the data processing unit 102 may also includea condition monitoring unit 215 in signal communication with theprocessor 204, and configured to monitor one or more physiological orother characteristics of the patient or the user of the data processingunit 102. For example, the perspiration level may be monitored by thecondition monitoring unit 215 in one embodiment by detecting ordetermining conductance signal levels that vary depending upon thepresence or absence of perspiration on skin, for example, usingelectrodes or probes or contacts on the skin of the patient. In oneaspect, the electrodes, probes or contacts to determine or monitor theone or more physiological characteristics such as level of perspirationmay be provided on the housing of the data processing unit 102, oralternatively, may be provided as a separate unit that is configured toprovide or transfer the monitored characteristics information or data tothe processor 204 of the data processing unit 102. Accordingly, in oneaspect, the microprocessor based logic provided to the processor 204 maybe configured to process the detected conductance signal levels todetermine the presence of absence of perspiration and/or, to determinethe level of and change in perspiration based on, for example, monitoredor detected conductance signal level.

Referring back to FIG. 2, the RF transmitter 206 of the data processingunit 102 may be configured for operation in a certain frequency band,e.g., the frequency band of 315 MHz to 322 MHz, for example, in theUnited States. The operating frequency band may vary depending upon thelocation of use, communication protocol used, components used toimplement the RF communication, and accordingly, the present disclosurecontemplates varying ranges of operating frequency bands. Further, incertain embodiments, the RF transmitter 206 is configured to modulatethe carrier frequency by performing, e.g., Frequency Shift Keying andManchester encoding, and/or other protocol(s). In certain embodiments,the data transmission rate is set for efficient and effectivetransmission. For example, in certain embodiments the data transmissionrate may be about 19,200 symbols per second, with a minimum transmissionrange for communication with the primary receiver unit 104.

Also shown is a leak detection circuit 214 coupled to the guard contact(G) 211 and the processor 204 in the data processing unit 102 of thedata monitoring and management system 100. The leak detection circuit214 may be configured to detect leakage current in the sensor 101 todetermine whether the measured sensor data is corrupt or whether themeasured data from the sensor 101 is accurate. Such detection maytrigger a notification to the user.

FIG. 3 shows a block diagram of an embodiment of a receiver/monitor unitsuch as the primary receiver unit 104 of the data monitoring andmanagement system shown in FIG. 1. The primary receiver unit 104 mayinclude one or more of: a blood glucose test strip interface 301 for invitro testing, an RF receiver 302, an input 303, a temperature detectionsection 304, and a clock 305, each of which is operatively coupled to aprocessing and storage section 307. The primary receiver unit 104 alsoincludes a power supply 306 operatively coupled to a power conversionand monitoring section 308. Further, the power conversion and monitoringsection 308 is also coupled to the receiver processor 307. Moreover,also shown are a receiver serial communication section 309, and anoutput 310, each operatively coupled to the processing and storage unit307. The receiver may include user input and/or interface components ormay be free of user input and/or interface components.

In certain embodiments having a test strip interface 301, the interfaceincludes a glucose level testing portion to receive a blood (or otherbody fluid sample) glucose test or information related thereto. Forexample, the interface may include a test strip port to receive an invitro glucose test strip. The device may determine the glucose level ofthe test strip, and optionally display (or otherwise report or output)the glucose level on the output 310 of the primary receiver unit 104.Any suitable test strip may be employed, e.g., test strips that onlyrequire a very small amount (e.g., one microliter or less, e.g., 0.5microliter or less, e.g., 0.1 microliter or less), of applied sample tothe strip in order to obtain accurate glucose information, e.g.FreeStyle® and Precision® blood glucose test strips from Abbott DiabetesCare Inc. Glucose information obtained by the in vitro glucose testingdevice may be used for a variety of purposes, computations, etc. Forexample, the information may be used to calibrate sensor 101 (however,calibration of the subject sensors may not be necessary), confirmresults of the sensor 101 to increase the confidence thereof (e.g., ininstances in which information obtained by sensor 101 is employed intherapy related decisions), etc. Exemplary blood glucose monitoringsystems are described, e.g., in U.S. Pat. Nos. 6,071,391; 6,120,676;6,338,790; and 6,616,819; and in U.S. application Ser. Nos. 11/282,001,now U.S. Pat. No. 7,918,975; and Ser. No. 11/225,659, now U.S. Pat. No.8,298,389, the disclosures of which are herein incorporated byreference.

The RF receiver 302 is configured to communicate, via the communicationlink 103 (FIG. 1) with the RF transmitter 206 of the data processingunit 102, to receive encoded data signals from the data processing unit102 for, among others, signal mixing, demodulation, and other dataprocessing. The input 303 of the primary receiver unit 104 is configuredto allow the user to enter information into the primary receiver unit104 as needed. In one aspect, the input 303 may include keys of akeypad, a touch-sensitive screen, and/or a voice-activated input commandunit, and the like. The temperature monitor section 304 is configured toprovide temperature information of the primary receiver unit 104 to thereceiver processing and storage unit 307, while the clock 305 provides,among others, real time information to the receiver processing andstorage unit 307.

Each of the various components of the primary receiver unit 104 shown inFIG. 3 is powered by the power supply 306 (and/or other power supply)which, in certain embodiments, includes a battery. Furthermore, thepower conversion and monitoring section 308 is configured to monitor thepower usage by the various components in the primary receiver unit 104for effective power management and may alert the user, for example, inthe event of power usage which renders the primary receiver unit 104 insub-optimal operating conditions. An example of such sub-optimaloperating condition may include, for example, operating the vibrationoutput mode (as discussed below) for a period of time thus substantiallydraining the power supply 306 while the processing and storage unit 307(thus, the primary receiver unit 104) is turned on. Moreover, the powerconversion and monitoring section 308 may additionally be configured toinclude a reverse polarity protection circuit such as a field effecttransistor (FET) configured as a battery activated switch.

The serial communication section 309 in the primary receiver unit 104 isconfigured to provide a bi-directional communication path from thetesting and/or manufacturing equipment for, among others,initialization, testing, and configuration of the primary receiver unit104. Serial communication section 309 can also be used to upload data toa computer, such as time-stamped blood glucose data. The communicationlink with an external device (not shown) can be made, for example, bycable, infrared (IR) or RF link. The output 310 of the primary receiverunit 104 is configured to provide, among others, a graphical userinterface (GUI) such as a liquid crystal display (LCD) for displayinginformation. Additionally, the output 310 may also include an integratedspeaker for outputting audible signals as well as to provide vibrationoutput as commonly found in handheld electronic devices, such as mobiletelephones, pagers, etc. In certain embodiments, the primary receiverunit 104 also includes an electro-luminescent lamp configured to providebacklighting to the output 310 for output visual display in dark ambientsurroundings.

Referring back to FIG. 3, the primary receiver unit 104 may also includea storage section such as a programmable, non-volatile memory device aspart of the processing and storage unit 307, or provided separately inthe primary receiver unit 104, operatively coupled to the processor. Theprocessing and storage unit 307 may be configured to perform Manchesterdecoding (or other protocol(s)) as well as error detection andcorrection upon the encoded data signals received from the dataprocessing unit 102 via the communication link 103.

In further embodiments, the data processing unit 102 and/or the primaryreceiver unit 104 and/or the secondary receiver unit 106, and/or thedata processing terminal/infusion section 105 may be configured toreceive the blood glucose value from a wired connection or wirelesslyover a communication link from, for example, a blood glucose meter. Infurther embodiments, a user manipulating or using the analyte monitoringsystem 100 (FIG. 1) may manually input the blood glucose value using,for example, a user interface (for example, a keyboard, keypad, voicecommands, and the like) incorporated in the one or more of the dataprocessing unit 102, the primary receiver unit 104, secondary receiverunit 106, or the data processing terminal/infusion section 105.

In certain embodiments, the data processing unit 102 (FIG. 1) isconfigured to detect the current signal from the sensor 101 (FIG. 1) andoptionally the skin and/or ambient temperature near the sensor 101,which may be preprocessed by, for example, the data processing unitprocessor 204 (FIG. 2) and transmitted to the receiver unit (forexample, the primary receiver unit 104 (FIG. 1)) at least at apredetermined time interval, such as for example, but not limited to,once per minute, once every two minutes, once every five minutes, oronce every ten minutes. Although specific time frames have beenmentioned, it is contemplated that the predetermined time interval maycorrespond to any amount of time selected by the patient, user orhealthcare provider. Additionally, the data processing unit 102 may beconfigured to perform sensor insertion detection and data qualityanalysis, information pertaining to which may also be transmitted to thereceiver unit 104 periodically at the predetermined time interval. Inturn, the receiver unit 104 may be configured to perform, for example,skin temperature compensation as well as calibration of the sensor datareceived from the data processing unit 102.

Additional detailed descriptions are provided in U.S. Pat. Nos.5,262,035; 5,262,035; 5,264,104; 5,262,305; 5,320,715; 5,593,852;6,103,033; 6,134,461; 6,175,752; 6,560,471; 6,579,690; 6,605,200;6,654,625; 6,746,582; and 6,932,894; and in U.S. Published PatentApplication No. 2004/0186365, now U.S. Patent No. 7,811,231, thedisclosures of which are herein incorporated by reference. Descriptionof exemplary methods for forming the sensor is provided in U.S. patentsand applications noted herein, including U.S. Patent Nos. 5,262,035;6,103,033; 6,175,752; and 6,284,478, the disclosures of which are hereinincorporated by reference. Examples of sensing layers that may beemployed are described in U.S. patents and applications noted herein,including, e.g., in U.S. Patent Nos. 5,262,035; 5,264,104; 5,543,326;6,605,200; 6,605,201; 6,676,819; and 7,299,082; the disclosures of whichare herein incorporated by reference.

The subject analyte measurement systems may include an alarm systemthat, e.g., based on information from a processor, warns the patient ofa potentially detrimental condition of the analyte. For example, ifglucose is the analyte, an alarm system may warn a user of conditionssuch as hypoglycemia and/or hyperglycemia and/or impending hypoglycemia,and/or impending hyperglycemia. An alarm system may be triggered whenanalyte levels approach, reach or exceed a threshold value. An alarmsystem may also, or alternatively, be activated when the rate of change,or the acceleration of the rate of change in the analyte level increaseor decrease, approaches, reaches or exceeds a threshold rate oracceleration. A system may also include system alarms that notify a userof system information such as battery condition, calibration, sensordislodgment, sensor malfunction, etc. Alarms may be, for example,auditory and/or visual. Other sensory-stimulating alarm systems may beused including alarm systems which heat, cool, vibrate, or produce amild electrical shock when activated.

The subject disclosure also includes sensors used in sensor-based drugdelivery systems. The system may provide a drug to counteract the highor low level of the analyte in response to the signals from one or moresensors. Alternatively, the system may monitor the drug concentration toensure that the drug remains within a desired therapeutic range. Thedrug delivery system may include one or more (e.g., two or more)sensors, a processing unit such as a transmitter, a receiver/displayunit, and a drug administration system. In some cases, some or allcomponents may be integrated in a single unit. A sensor-based drugdelivery system may use data from the one or more sensors to providenecessary input for a control algorithm/mechanism to adjust theadministration of drugs, e.g., automatically or semi-automatically. Asan example, a glucose sensor may be used to control and adjust theadministration of insulin from an external or implanted insulin pump.

Referring back to the Figures, FIG. 4 is a flowchart illustrating aroutine associated with determining false signal attenuation of ananalyte sensor in one aspect of the present disclosure. As shown, in oneembodiment, a rate of change of analyte level such as monitored glucoselevel variation is determined or compared against a predeterminedthreshold level (410). In one aspect, the predetermined threshold levelmay be pre-programmed and stored in a memory storage device of the dataprocessing unit 102 (FIG. 1) and/or the processing and storage unit 307(FIG. 3) of the receiver 104/106. In other aspects, the predeterminedthreshold level may be programmable or adjustable by the user or thehealthcare provider. In still a further aspect, the predeterminedthreshold level may include a plurality of threshold levels, eachcorresponding to a particular time of day (for example, day time, mealtime, or night time) or an event such as exercise, meal, sleeping,intake of medication and the like.

Referring again to FIG. 4, when it is determined that the rate of changeof the monitored analyte level crosses a predetermined threshold level(410) (for example, by exceeding an upper threshold level, or by fallingbelow a lower threshold level), a temporary hold assertion function iscalled and executed to temporarily hold the assertion of a programmednotification based on the detected analyte level rate of change (420).That is, in one aspect, when an alarm or alert notification isprogrammed to be asserted based on the analyte level rate of changecrossing the predetermined threshold, before the assertion of the alarmor alert notification is implemented, the receiver 104 or the dataprocessing unit 102 may be programmed to execute a hold function totemporarily hold off the assertion of the alarm/alert notification.

Thereafter, as shown in FIG. 4, a rate of change or variation of anothermonitored parameter is compared against a predetermined limit(pre-programmed or adjusted by the user or the healthcare provider) todetermine whether the rate of change of the monitored parameter crossesthe predetermined limit (430). That is, in one aspect, a monitoredtemperature and/or perspiration level is retrieved and the rate ofchange of the temperature level is determined and compared against thepredetermined limit. In one aspect, the time period of determining therate of change of the monitored parameter is programmed or set tocoincide with the time period of the monitored analyte level (based onwhich the alarm/alert notification is initiated). While the level oftemperature or perspiration is described above as the monitoredparameter which is determined upon detection of an alarm/alertnotification based on the analyte level rate of change, within the scopeof the present disclosure, other physiological and/or environmentalparameters may be determined or analyzed individually, or in combinationwith one or more of the temperature level or the perspiration level.

Based on the determination of whether the rate of change of themonitored parameter crosses the predetermined limit (430), thepresence/absence or onset of a medically significant conditionassociated with the alarm/alert notification discussed above, isconfirmed (440), and thereafter upon confirmation of the presence of themedically significant condition, the hold assertion function is removedand the alarm/alert notification is output to, for example, notify theuser or the healthcare provider (450). In one embodiment, thealarm/alert notification may include one or more of an audiblenotification (a discrete sound or a series of sounds or tones thateither vary in intensity and/or output level), a vibratory notification(which may increase/decrease in the strength of vibration or bemaintained at a steady vibration strength), or a visual notification (anumeric, graphical, textual or combinations thereof).

In this manner, in one aspect of the present disclosure, upon detectionof a medically significant condition such as a hypoglycemic conditionbased on the monitored analyte levels, before any alarm or alertnotification is output or presented to the user to take correctiveactions, the detection of such condition is confirmed based on one ormore other monitored parameters such as the level or variation of theuser's body or on-skin temperature or the level or variation inperspiration. In this manner, the potential for a false positiveindication of such alarm or alert condition determined based on themonitored analyte level alone may be reduced by confirmation of suchcondition based on other physiological and/or environmental parametersassociated with the user.

Moreover, while hypoglycemia is described above, the medicallysignificant condition may include other physiological conditions of theuser where supplemental or additional monitored parameters are used toconfirm the presence of the medically significant condition prior tonotifying the user. Accordingly, the frequency of the false indicationof the medically significant condition presence can be reduced and also,the user may be prevented from taking unnecessary corrective actionsbased on false indications of such condition.

FIG. 5 is a flowchart illustrating a routine associated with determiningfalse signal attenuation of an analyte sensor in another aspect of thepresent disclosure. Referring to the Figure, in one aspect, when theinitiation of hypoglycemic condition notification is detected (510), ahold condition to the notification is applied and the monitoredtemperature information is retrieved (520). Thereafter, the rate ofchange of the retrieved temperature level is compared to a thresholdlevel (530). If it is determined that the determined rate of temperaturelevel change crosses the threshold (530), then the hold condition isremoved and the initiated hypoglycemic notification is asserted (540).On the other hand, if the determined rate of temperature level change isdetermined to not have crossed the threshold (530), then the holdcondition is maintained and the initiated hypoglycemic notification isdeactivated (550).

Referring back to FIG. 5, when the monitored temperature information isretrieved (520), in one embodiment, the time period of the retrievedmonitored temperature information is determined to substantiallycoincide with the time period of monitored analyte level based on whichthe hypoglycemic condition notification is initiated (510). In analternate embodiment, the time period of the retrieved monitoredtemperature information may include the time period of the monitoredanalyte level such that the monitored temperature for processing and/oranalysis spans a wider time period range.

Still alternatively, the time period of the monitored temperatureinformation may be a subset of the time period of the monitored analytelevel based on which the hypoglycemic condition notification isinitiated. Indeed, the variation in the monitored time period as well asthe number of available data sets for the monitored temperature leveland the monitored analyte level may vary based on one or more of thefrequency of data sampling, the availability of the information, thedegree of sensitivity of the temperature detection (e.g., thermistor),and the like.

FIG. 6 is a flowchart illustrating a routine associated with determiningfalse signal attenuation of an analyte sensor in a further aspect of thepresent disclosure. As shown, in one embodiment, a plurality of timespaced analyte sensor data during a first time period is received (610).Thereafter, a plurality of time spaced on-skin temperature data duringthe first time period is received (620). Upon detection of a rapiddecline in the received plurality of time spaced analyte sensor dataduring the first time period (630), the plurality of time spaced on-skintemperature data is analyzed. In one aspect, rapid decline in thereceived plurality of time spaced analyte sensor data may include a rateof change of the analyte sensor data at or greater than 2 mg/dL/min.Within the scope of the present disclosure, the rapid decline mayinclude other variations of the rate of change that is greater or lessthan 2 mg/dL/min. Furthermore, while on skin temperature levelmonitoring and detection is described above, in accordance with aspectsof the present disclosure, any suitable body temperature may be measuredand used to confirm or reject the preliminary indication of ahypoglycemic condition.

Referring back to FIG. 6, upon detection of a steady state condition ofthe received plurality of time spaced temperature data during the firsttime period (640), low glucose alarm function (for example, in the dataprocessing unit 102 and/or the receiver unit 104/106, or the dataprocessing terminal/infusion section 105) is disabled (650) indicatingthat the detected rapid decline in the received plurality of time spacedanalyte sensor data during the first time period (630) is not associatedwith a low glucose condition (or glucose level trending towards a lowglucose condition), but rather, a false indication of the low glucosecondition or an analyte sensor signal attenuation which may beattributable to parameters associated with the analyte sensor (e.g.,unstable sensor), errors in data processing, dislodged sensor or thelike. In one aspect, the steady state condition of the receivedplurality of time spaced temperature data may include variation of thetemperature data during the first time period that does not cross apredetermined or preset level. That is, a steady state condition mayinclude a relatively stable temperature information or level during thefirst time period.

While monitoring glucose level in addition to monitoring and determiningtemperature and/or perspiration level as described in conjunction withthe various aspects of the present disclosure, other physiologicalparameters may be monitored and used to confirm or reject the occurrenceof hypoglycemic condition. For example, palpitation or variation inheart rate may be monitored using, for example, a heart rate monitor, orthe oxygen saturation level may be monitored using, for example, a pulseoximeter, to confirm or reject the occurrence of hypoglycemic conditionindicated by the monitored glucose levels. Additional description ofpulse oximetry for monitoring oxygen saturation level is provided inU.S. Pat. Nos. 6,606,511 and 6,912,413, disclosures of each of which areincorporated herein by reference. Furthermore, description of heart ratemonitors for monitoring the heart rate is provided in U.S. Pat. No.6,549,756, the disclosure of which is incorporated herein by reference.

Additionally, tremor may be monitored to confirm the detection ofhypoglycemic condition where a variation in the movement may be used toconfirm or reject the occurrence of hypoglycemic condition. Additionaldescription of detecting tremor is provided in U.S. Pat. No. 5,293,879,the disclosure of which is incorporated herein by reference.Accordingly, when the monitored glucose level received from the analytesensor indicates a hypoglycemic condition (or an impending hypoglycemiccondition), a detection or variation of one or more of tremor,palpitation, perspiration, temperature or other physiological parametersmay be used to in conjunction with the sensor data confirm or reject theindication of hypoglycemic condition.

FIG. 7 is a graphical illustration of the monitored glucose level andthe corresponding temperature level during the same time periodconfirming a hypoglycemic event. In contrast, FIG. 8 provides agraphical illustration of the monitored glucose level and thecorresponding temperature level during the same time period indicating afalse hypoglycemic event. As shown in these graphical illustrations, inaspects of the present disclosure, when an actual analyte sensor signalattenuation is detected (indicating a low glucose level), the level ofthe supplemental or additional parameter such as the temperature levelis similar attenuated providing a level of correlation between thedirection of change of the analyte level and the temperature level (asshown in FIG. 7).

On the other hand, as shown in FIG. 8, if the analyte sensor signalreported by the sensor is a false indication of the monitored analytelevel, the corresponding level of the monitored additional parametersuch as the temperature level does not provide the level of correlationas discussed above, but rather, indicates a deviation in the directionof change compared to the direction of change of the monitored analytelevel.

In the manner described, in accordance with the various embodiments ofthe present disclosure, the occurrence of false alarms associated withanalyte sensor signal attenuation may be minimized or mitigated bycorrelating the monitored analyte level with one or more additionalparameters such as temperature or perspiration level. Accordingly, alarmor alert functions associated with monitored analyte levels inaccordance with the present disclosure may be asserted when theunderlying conditions associated with the alarm or alert functionaccurately reflects the monitored condition such that the user or thepatient is not prompted to take unnecessary corrective actions based onfalse indication of the monitored condition.

The various processes described above including the processes operatingin the software application execution environment in the analytemonitoring system 100 including the data processing unit 102, thereceiver unit 104/106 or the data processing terminal/infusion section105, performing one or more routines associated with the false analytesensor signal attenuation determination described in conjunction withFIGS. 4-6, may be embodied as computer programs developed using anobject oriented language that allows the modeling of complex systemswith modular objects to create abstractions that are representative ofreal world, physical objects and their interrelationships. The softwarerequired to carry out the inventive process, which may be stored in amemory or storage device of the storage unit of the data processing unit102, the receiver unit 104/106 or the data processing terminal/infusionsection 105 in the analyte monitoring system 100, may be developed by aperson of ordinary skill in the art and may include one or more computerprogram products.

In one embodiment, a method may include receiving a plurality of timespaced analyte related data monitored by an analyte sensor in fluidcontact with an analyte during a first time period, detecting when oneor more of the received plurality of time spaced analyte related datacrosses a predetermined analyte threshold level during the first timeperiod, receiving a plurality of time spaced temperature data during thefirst time period, determining a rate of change of the receivedplurality of time spaced temperature data, detecting when the determinedrate of change crosses a predetermined rate of temperature change, andasserting a notification when the determined rate of change of thereceived plurality of the time spaced temperature data reaches thepredetermined rate of temperature change and when the one or more of thereceived plurality of time spaced analyte related data reaches thepredetermined threshold analyte level during the first time period.

A further embodiment may include determining when the monitored analytelevel based on the received plurality of time spaced analyte relateddata indicates approaching the predetermined analyte threshold levelduring a second time period.

The first time period may precede the second time period.

The asserted notification may include one or more of an audible alert, avibratory alert, a visual alert, or one or more combinations thereof

The predetermined analyte threshold level may be associated with one ofan impending hypoglycemic condition or an onset of hypoglycemiccondition.

Another aspect may include determining a rate of change of the receivedplurality of time spaced analyte related data and comparing a slope ofthe determined rate of change of the received plurality of time spacedanalyte related data to a slope of the rate of change of the receivedplurality of time spaced temperature data.

The slope of the determined rate of change of the received plurality ofanalyte related data and the slope of the rate of change of the receivedplurality of time spaced temperature data may be coincident.

The asserted notification may include an impending hypoglycemiccondition.

Yet another aspect may include when the determined rate of change of thereceived plurality of the time spaced temperature data does not exceedthe predetermined rate of temperature change, deactivating anotification function.

The deactivated notification function may include a hypoglycemic alarm.

Another embodiment may comprise receiving a plurality of time spacedanalyte related data monitored by an analyte sensor in fluid contactwith an analyte during a first time period, detecting when one or moreof the received plurality of time spaced analyte related data crosses apredetermined analyte threshold level during the first time period,receiving a plurality of time spaced temperature data during the firsttime period, detecting when one or more of the time spaced temperaturerelated data crosses a predetermined threshold temperature level duringthe first time period, and asserting a notification when the one or moreof the received plurality of time spaced analyte related data reaches apredetermined threshold analyte level and when the one or more of theplurality of time spaced temperature related data reaches thepredetermined temperature threshold level during the first time period.

Another embodiment may further include determining when the monitoredanalyte level based on the received plurality of time spaced analyterelated data indicates approaching the predetermined analyte thresholdlevel during a second time period.

The first time period may precede the second time period.

The asserted notification may be associated with a medically significantcondition.

The medically significant condition may include an impendinghypoglycemic condition.

Yet another embodiment may comprise monitoring a variation in on-skintemperature in proximity to a transcutaneously positioned analyte sensorhaving at least a portion in fluid contact with an analyte during amonitoring time period, detecting the variation in the monitoredtemperature exceeding a predetermined threshold level, confirming apresence of a medically significant condition when the detectedvariation in the monitored temperature exceeds the predeterminedthreshold level, and asserting a notification associated with themedically significant condition when it is confirmed, wherein confirmingthe presence of the medically significant condition includes determininga variation in the monitored analyte level exceeding the predeterminedthreshold level based on comparing a slope indicative of the change inthe monitored analyte level substantially to a slope indicative of thechange in the monitored on-skin temperature variation.

In yet another embodiment, a method may comprise detecting a concurrentoccurrence of a decrease in monitored analyte level and a correspondingdecrease in monitored on-skin temperature, confirming a presence of animpending hypoglycemic condition, and asserting a notificationcorresponding to the confirmed impending hypoglycemic condition.

The decrease in the monitored analyte level may include a decreaseexceeding approximately 2 mg/dL/minute.

The decrease in the monitored on-skin temperature may include atemperature decrease exceeding approximately 2° C./15 minutes.

Detecting the concurrent occurrence may include determining a rate ofchange of the monitored analyte level during a predetermined timeperiod, determining a rate of change of the monitored on-skintemperature during the predetermined time period, and verifying thedetermined rate of change of the monitored analyte level and thedetermined rate of change of the monitored on-skin temperature exceeds apredetermined threshold level substantially at the same time.

In another embodiment, a method of confirming hypoglycemic condition ina patient may comprise monitoring a directional change in glucose levelbased on data stream received from an analyte sensor during a monitoringtime period, monitoring a directional change in a first physiologicalparameter during the monitoring time period, monitoring a directionalchange in a second physiological parameter during the monitoring timeperiod, detecting an initialization of a hypoglycemic alarm based, atleast in part, on the directional change of the monitored glucose level,and comparing the directional change in one or more of the first or thesecond physiological parameters relative to the directional change inthe glucose level prior to the assertion of the hypoglycemic alarm.

The first physiological parameter or the second physiological parametermay be one of a temperature level, a perspiration level, heart rate,detected tremor, or oxygen saturation level.

The hypoglycemic alarm may be asserted when the glucose leveldirectional change and the first physiological parameter directionchange are the same.

The alarm may be asserted only when the second physiological parameterdirectional change is opposite the first physiological parameterdirectional change.

The monitored directional change in glucose level may have a negativeslope.

The monitored directional change in the first physiological parametermay have a negative slope, and further, the monitored directional changein the second physiological parameter may have a positive slope.

The monitoring time period may include approximately five days or sevendays.

The hypoglycemic alarm initialization may be detected when the monitoreddirectional change in glucose level exceeds a predetermined threshold.

The predetermined threshold may include a decreasing rate of glucoselevel of approximately 2 mg/dL/minute.

Comparing the directional change may include temporarily disabling thehypoglycemic alarm initialization based on the comparison.

The hypoglycemic alarm initialization may be disabled when thedirectional change of the first and second physiological parameters arethe same.

The hypoglycemic alarm initialization may be disabled when thedirectional change of the monitored glucose level does not coincide withthe directional change of either of the first and second physiologicalparameters.

In another embodiment, an apparatus may comprise one or more processorsand a memory for storing instructions which, when executed by the one ormore processors, causes the one or more processors to receive aplurality of time spaced analyte related data monitored by an analytesensor in fluid contact with an analyte during a first time period,determine a rate of change of the received plurality of time spacedanalyte related data, receive a plurality of time spaced temperaturedata during the first time period, determine a rate of change of thereceived plurality of time spaced temperature data, compare thedetermined rate of change of the received plurality of the time spacedtemperature data to the predetermined threshold level when thedetermined rate of change of the received plurality of time spacedanalyte related data exceeds a predetermined threshold level, and asserta notification when the determined rate of change of the receivedplurality of the time spaced temperature data exceeds the predeterminedthreshold level.

The asserted notification may include one or more of an audible alert, avibratory alert, a visual alert, or one or more combinations thereof

The predetermined threshold level may include 3% decrease between eachadjacent time spaced analyte related data and 3% decrease between eachadjacent time temperature data.

The determined rate of change of the received plurality of time spacedanalyte related data and the determined rate of change of the receivedplurality of time spaced temperature data may be temporally coincident.

The asserted notification may be associated with a medically significantcondition.

The medically significant condition may include an impendinghypoglycemic condition.

The notification may be asserted only when the determined rate of changeof the received plurality of time spaced temperature data and thedetermined rate of change of the received analyte related data exceedsthe predetermined threshold level substantially at the same time duringthe first time period.

The first time period may correspond to an analyte sensor life.

A further aspect may include when the determined rate of change of thereceived plurality of the time spaced temperature data does not exceedthe predetermined threshold level, deactivating a notification functionconfigured to be asserted when the determined rate of change of theanalyte related data exceeds the predetermined threshold level.

The deactivated notification function may include a hypoglycemic alarm.

In another embodiment, an apparatus may comprise one or more processors,and a memory for storing instructions which, when executed by the one ormore processors, causes the one or more processors to monitor avariation in on-skin temperature in proximity to a transcutaneouslypositioned analyte sensor having at least a portion in fluid contactwith an analyte during a monitoring time period, detect the variation inthe monitored temperature exceeding a predetermined threshold level,confirm a presence of a medically significant condition when thedetected variation in the monitored temperature exceeds thepredetermined threshold level, and assert a notification associated withthe medically significant condition when it is confirmed, wherein thememory for storing instructions which, when executed by the one or moreprocessors, causes the one or more processors to determine a variationin the monitored analyte level exceeding the predetermined thresholdlevel based on comparing a slope indicative of the change in themonitored analyte level substantially to a slope indicative of thechange in the monitored on-skin temperature variation.

Yet another embodiment may include an apparatus comprising one or moreprocessors, and a memory for storing instructions which, when executedby the one or more processors, causes the one or more processors todetect a concurrent occurrence of a decrease in monitored analyte leveland a corresponding decrease in monitored on-skin temperature, confirm apresence of an impending hypoglycemic condition, and assert anotification corresponding to the confirmed impending hypoglycemiccondition.

The decrease in the monitored analyte level may include a decreaseexceeding approximately 2 mg/dL/minute.

The decrease in the monitored on-skin temperature may include atemperature decrease exceeding approximately 2° C./15 minutes.

The memory for storing instructions which, when executed by the one ormore processors, may cause the one or more processors to determine arate of change of the monitored analyte level during a predeterminedtime period, determine a rate of change of the monitored on-skintemperature during the predetermined time period, and verify thedetermined rate of change of the monitored analyte level and thedetermined rate of change of the monitored on-skin temperature exceeds apredetermined threshold level substantially at the same time.

In yet another embodiment, an apparatus may comprise one or moreprocessors, and a memory for storing instructions which, when executedby the one or more processors, causes the one or more processors tomonitor a directional change in glucose level based on data streamreceived from an analyte sensor during a monitoring time period, monitora directional change in a first physiological parameter during themonitoring time period, monitor a directional change in a secondphysiological parameter during the monitoring time period, detect aninitialization of a hypoglycemic alarm based, at least in part, on thedirectional change of the monitored glucose level, and compare thedirectional change in one or more of the first or the secondphysiological parameters relative to the directional change in theglucose level prior to the assertion of the hypoglycemic alarm.

The first physiological parameter or the second physiological parametermay be one of a temperature level, a perspiration level, heart rate,detected tremor, or oxygen saturation level.

The hypoglycemic alarm may be asserted when the glucose leveldirectional change and the first physiological parameter directionalchange are the same.

The alarm may be asserted only when the second physiological parameterdirectional change is opposite the first physiological parameterdirectional change.

The monitored directional change in glucose level may have a negativeslope.

The monitored directional change in the first physiological parametermay have a negative slope, and further, the monitored directional changein the second physiological parameter may have a positive slope.

The monitoring time period may include approximately five days or sevendays.

The hypoglycemic alarm initialization may be detected when the monitoreddirectional change in glucose level exceeds a predetermined threshold.

The predetermined threshold may include a decreasing rate of glucoselevel of approximately 2 mg/dL/minute.

The memory for storing instructions which, when executed by the one ormore processors, may cause the one or more processors to temporarilydisable the hypoglycemic alarm initialization based on the comparison.

The memory for storing instructions which, when executed by the one ormore processors, may cause the one or more processors to disable thehypoglycemic alarm initialization when the directional change of thefirst and second physiological parameters are the same.

The memory for storing instructions which, when executed by the one ormore processors, may cause the one or more processors to disable thehypoglycemic alarm initialization when the directional change of themonitored glucose level does not coincide with the directional change ofeither of the first and second physiological parameters.

Various other modifications and alterations in the structure and methodof operation of this invention will be apparent to those skilled in theart without departing from the scope and spirit of the invention.Although the invention has been described in connection with specificpreferred embodiments, it should be understood that the invention asclaimed should not be unduly limited to such specific embodiments. It isintended that the following claims define the scope of the presentinvention and that structures and methods within the scope of theseclaims and their equivalents be covered thereby.

What is claimed is:
 1. A system, comprising: an analyte sensorpositioned in fluid contact with interstitial fluid under a skin layerand configured to generate signals corresponding to a monitored analytelevel in the interstitial fluid; sensor electronics electrically coupledto the analyte sensor and configured to generate analyte data based onthe signals generated by the analyte sensor; and a data receiverconfigured to receive the generated analyte data from the sensorelectronics, the data receiver configured to trigger a hold assertionfunction to prevent the assertion of a programmed notification when arate of change of the monitored analyte level determined from thegenerated analyte data exceeds a predetermined analyte threshold duringa monitoring time period, and to assert the programmed notification whenthe rate of change of a monitored temperature exceeds a predeterminedtemperature threshold during the monitoring time period.
 2. The systemof claim 1, wherein the predetermined analyte threshold includes adecreasing rate of the analyte level of approximately 2 mg/dL/minute. 3.The system of claim 1, wherein the asserted programmed notificationindicates a hypoglycemic condition.
 4. The system of claim 1, whereinthe data receiver is configured to assert the programmed notificationwhen a direction of the analyte level rate of change and a direction ofthe monitored temperature rate of change are the same.
 5. The system ofclaim 1, wherein the monitored analyte level includes one or more ofglucose level or lactate level.
 6. The system of claim 1, wherein thedata receiver is configured to receive monitored temperature informationto determine the rate of change of the monitored temperature.
 7. Thesystem of claim 1, wherein the predetermined temperature thresholdincludes a decreasing rate of a temperature level of approximately 2°C./15 minutes.
 8. The system of claim 1, wherein the analyte sensorincludes a plurality of electrodes including a working electrodecomprising an analyte-responsive enzyme bonded to a polymer disposed onthe working electrode.
 9. The system of claim 8, wherein theanalyte-responsive enzyme is chemically bonded to the polymer disposedon the working electrode.
 10. The system of claim 8, wherein the workingelectrode comprises a mediator bonded to the polymer disposed on theworking electrode.
 11. The system of claim 10, wherein the mediator iscrosslinked with the polymer disposed on the working electrode.
 12. Thesystem of claim 1, wherein the analyte sensor includes a plurality ofelectrodes including a working electrode comprising a mediator bonded toa polymer disposed on the working electrode.
 13. A system, comprising:sensor electronics configured to receive signals from an analyte sensorin fluid contact with interstitial fluid, and to generate analyte datacorresponding to a monitored anlayte level in interstitial fluid; and adata receiver configured to receive the generated analyte data from thesensor electronics, the data receiver configured to prevent theassertion of a programmed notification when a rate of change of themonitored analyte level determined from the generated analyte dataexceeds a predetermined analyte threshold during a monitoring timeperiod, but to assert the programmed notification when a rate of changeof the monitored temperature exceeds a predetermined temperaturethreshold during the monitoring time period.
 14. The system of claim 13,wherein the predetermined analyte threshold includes a decreasing rateof the analyte level of approximately 2 mg/dL/minute.
 15. The system ofclaim 13, wherein the predetermined temperature threshold includes adecreasing rate of a temperature level of approximately 2° C./15minutes.
 16. The system of claim 13, wherein the data receiver isconfigured to assert the programmed notification when the direction ofthe analyte level rate of change and the direction of the temperaturelevel rate of change are the same.